{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:24:54Z","timestamp":1788866694374,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00246"],"award-info":[{"award-number":["PI20\/00246"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/00109"],"award-info":[{"award-number":["PI22\/00109"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/00684"],"award-info":[{"award-number":["PI22\/00684"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2025,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n To investigate the prognostic value of maternal angiogenic factors in late\u2010onset small fetuses, alone or in combination with the ultrasound and Doppler parameters currently used for the classification of low\u2010risk small\u2010for\u2010gestational\u2010age (SGA) fetuses or high\u2010risk fetal growth restriction (FGR), overall and according to the presence or absence of pre\u2010eclampsia.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This was a prospective cohort study of women with a singleton pregnancy with a diagnosis of late\u2010onset fetal smallness (defined as birth weight <\u200910\n th<\/jats:sup>\n centile) and a gestational age of \u2265\u200934\u2009weeks at delivery. Ultrasound assessment of estimated fetal weight (EFW) and Doppler assessment of uterine artery pulsatility index (UtA\u2010PI) and cerebroplacental ratio (CPR) were performed every 1\u20132\u2009weeks. Biochemical analysis of the angiogenic factors placental growth factor (PlGF) and soluble fms\u2010like tyrosine kinase\u20101 (sFlt\u20101) in maternal peripheral venous blood samples was performed using enzyme\u2010linked immunosorbent assay within 1\u20132\u2009weeks after diagnosis of SGA or FGR. The primary outcome was adverse perinatal outcome, defined as a composite of emergency Cesarean section for non\u2010reassuring fetal status, metabolic acidosis (umbilical artery pH <\u20097.0), neonatal unit admission and\/or perinatal death. The predictive value of EFW <\u20093\n rd<\/jats:sup>\n \u2009centile, Doppler parameters (UtA\u2010PI >\u200995\n th<\/jats:sup>\n \u2009centile and CPR <\u20095\n th<\/jats:sup>\n \u2009centile) and sFlt\u20101\/PlGF ratio >\u200995\n th<\/jats:sup>\n \u2009centile, alone or in combination, was assessed using logistic regression analysis in the overall population and stratified by presence or absence of pre\u2010eclampsia developing at any time before delivery.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among the 602 included cases, 91 (15.1%) developed pre\u2010eclampsia and 511 (84.9%) did not. In the overall study population, all parameters were associated independently with adverse perinatal outcome: EFW <\u20093\n rd<\/jats:sup>\n \u2009centile (adjusted odds ratio (aOR), 2.58 (95%\u2009CI, 1.67\u20134.00)), UtA\u2010PI >\u200995\n th<\/jats:sup>\n \u2009centile (aOR, 1.92 (95%\u2009CI, 1.25\u20132.94)), CPR <\u20095\n th<\/jats:sup>\n \u2009centile (aOR, 2.35 (95%\u2009CI, 1.46\u20133.78)) and sFlt\u20101\/PlGF ratio >\u200995\n th<\/jats:sup>\n \u2009centile (aOR, 1.71 (95%\u2009CI, 1.09\u20132.69)). Only sFlt\u20101\/PlGF ratio >\u200995\n th<\/jats:sup>\n \u2009centile was associated independently with adverse perinatal outcome in cases with pre\u2010eclampsia, whereas in those without pre\u2010eclampsia, only EFW <\u20093\n rd<\/jats:sup>\n \u2009centile and CPR <\u20095\n th<\/jats:sup>\n \u2009centile were associated independently with adverse perinatal outcome. In the overall population, the detection rate (DR) and false\u2010positive rate for adverse perinatal outcome were, respectively: 39.8% (95%\u2009CI, 31.7\u201347.9%) and 16.9% (95%\u2009CI, 10.7\u201323.1%) for sFlt\u20101\/PlGF ratio >\u200995\n th<\/jats:sup>\n \u2009centile alone; 86.8% (95%\u2009CI, 83.4\u201390.2%) and 61.9% (95%\u2009CI, 57.1\u201366.7%) for a combined model of EFW <\u20093\n rd<\/jats:sup>\n \u2009centile, UtA\u2010PI >\u200995\n th<\/jats:sup>\n \u2009centile and CPR <\u20095\n th<\/jats:sup>\n \u2009centile; 81.3% (95%\u2009CI, 77.3\u201385.3%) and 52.3% (95%\u2009CI, 47.1\u201357.5%) for a combined model of EFW <\u20093\n rd<\/jats:sup>\n \u2009centile and sFlt\u20101\/PlGF ratio >\u200995\n th<\/jats:sup>\n \u2009centile; and 88.5% (95%\u2009CI, 85.4\u201391.6%) and 64.5% (95%\u2009CI, 59.8\u201369.2%) for a combined model including all the abovementioned observed parameters.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n sFlt\u20101\/PlGF ratio alone had a low predictive value for adverse perinatal outcome, but when combined with EFW, its predictive performance was similar to that of EFW combined with Doppler parameters. Combining sFlt\u20101\/PlGF ratio with EFW and Doppler criteria achieved the highest DR for adverse perinatal outcome, and additionally, might help to identify imminent pre\u2010eclampsia in pregnancies complicated by fetal smallness. These findings support the use of angiogenic factors as an additional criterion to those currently used for identifying high\u2010risk FGR among late\u2010onset small fetuses, but do not support their use as a standalone biomarker. \u00a9 2025 The Author(s).\n Ultrasound in Obstetrics & Gynecology<\/jats:italic>\n published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/uog.29181","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T07:44:12Z","timestamp":1738223052000},"page":"317-324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Angiogenic factors alone or in combination with ultrasound Doppler criteria for risk classification among late\u2010onset small fetuses with or without pre\u2010eclampsia"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-5507","authenticated-orcid":false,"given":"L.","family":"Youssef","sequence":"first","affiliation":[{"name":"BCNatal, Barcelona Center for Maternal\u2010Fetal and Neonatal Medicine, Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u, IDIBAPS University of Barcelona Barcelona Spain"},{"name":"Josep Carreras Leukemia Research Institute Hospital Clinic, University of Barcelona Campus Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7422-5240","authenticated-orcid":false,"given":"F.","family":"Crispi","sequence":"additional","affiliation":[{"name":"BCNatal, Barcelona Center for Maternal\u2010Fetal and Neonatal Medicine, Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u, IDIBAPS University of Barcelona Barcelona Spain"},{"name":"Center for Biomedical Research on Rare Diseases (CIBER\u2010ER) Madrid 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